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Abstract

Background Mitral valve replacement (MVR) has a high mortality and morbidity. It has been suggested that preservation of the subvalvular apparatus and more optimal timing of surgery might improve outcome.

Methods and Results We performed a retrospective study of 612 consecutive patients who underwent mitral valve repair or replacement: 226 patients had repair, 68 had replacement with subvalvular preservation (MVR/SVP), and 318 had replacement without subvalvular preservation (MVR/NoSVP). Baseline characteristics were most unfavorable in the repair group with respect to age (P=.002) and in the repair and MVR/SVP groups with respect to NYHA functional class and left ventricular function (P=.044). Thirty-day mortality was lower in the repair (1.8%, P=.046) and MVR/SVP (1.5%, P=NS) groups than the MVR/NoSVP group (5.0%). Overall survival at 7 years was better in the repair (71.2±5.6%, P=.022) and MVR/SVP (66.2±12.4%, P=.017) groups than the MVR/NoSVP group (63.5±3.4%). Myocardial failure caused 66 of 107 complication-related deaths. Multivariate analysis confirmed independent beneficial effects of repair on 30-day mortality (odds ratio, 0.27, P<.05) and of repair and MVR/SVP on overall mortality (hazard ratios, 0.43, P<.001 and 0.40, P<.05, respectively) and complication-related death (hazard ratios, 0.38, P<.001 and 0.35, P<.05, respectively). Preoperative NYHA class III or IV symptoms and left ventricular impairment were independent risk factors for death and myocardial failure.

Conclusions Mitral valve repair is superior to replacement. If repair is not feasible, the subvalvular apparatus should be preserved. Early surgery before the development of severe symptoms and demonstrable left ventricular impairment is also needed to optimize outcome.

Current evidence suggests that mitral valve repair is superior to replacement.123456789 Preservation of the subvalvular apparatus maintains LV function and thus improves survival.6 Repair is not always feasible or successful, particularly with rheumatic valve disease in young patients910 and severely disorganized valves. Such patients need valve replacement. Their survival may be improved by subvalvular preservation1112 or, if preservation is impossible, implantation of artificial chordae tendineae.13 These techniques are not in widespread routine use despite studies showing better results from repair123456 and replacement with subvalvular preservation.1112 Their true value has been obscured by limited numbers of comparative studies, most of which involved small numbers of patients with repair1 or replacement with subvalvular preservation,1114 did not distinguish between replacement with and without subvalvular preservation,115 were not randomized, or failed to account for differences in baseline patient characteristics by multivariate analysis.1 LV function has been used as a surrogate end point,6 but the effects of different surgical procedures on clinical myocardial failure have not been formally assessed. Suboptimal timing of surgery is a major cause of postoperative myocardial failure,16 but the magnitude of the problem has not been specifically quantified. We therefore performed univariate and multivariate analyses of clinical outcome in 612 consecutive patients who underwent mitral valve repair or replacement with or without subvalvular preservation, with particular emphasis on clinical myocardial failure.

Methods

Patients and Surgery

Our study population comprised 612 consecutive patients who underwent mitral valve repair (226 patients), MVR/SVP (68 patients), or MVR/NoSVP (318 patients) for degenerative, rheumatic, or endocarditic mitral valve disease between January 1987 and June 1994. Mean age was 63.4±10.4 years and mean follow-up, 41.7±28.8 months. Twenty-three patients moved away, but follow-up data were available until the time of their departure, and subsequent deaths were traced through the Office of Population Censuses and Surveys.

Mitral valves judged on preoperative assessment to be reparable were referred by experienced cardiologists to one surgeon with a special interest in repair. The remainder were distributed randomly between this and three other experienced surgeons for valve replacement. The proportion of patients who actually underwent repair increased with increasing surgical experience and reached a stable plateau by 1990. There was no policy favoring MVR/SVP, which was performed randomly in suitable patients. Bioprostheses were implanted in 6 patients (8.8%) in the MVR/SVP group and in 65 (20.7%) in the MVR/NoSVP group, mainly in patients >65 years old. Valve replacement for mitral stenosis was performed only for mitral restenosis after previous surgical valvotomy or if repair or valvotomy was not feasible or was unsuccessful. Concomitant ischemic heart disease was defined as previous myocardial infarction or angiographic coronary artery stenosis of >60% arterial diameter in at least one large vessel. All patients underwent preoperative coronary angiography. Concomitant ischemic heart disease was present in 103 patients, and concomitant bypass graft surgery was performed in all 93 patients with coronary stenoses of ≥60% arterial diameter. The other 10 patients had only minor coronary stenoses and a history of myocardial infarction (2 in the repair group, 2 in the MVR/SVP group, and 6 in the MVR/NoSVP group). All 119 patients with hemodynamically significant concomitant aortic valve disease underwent concomitant aortic valve replacement. Surgical techniques, myocardial protection, and types of prostheses used were similar throughout the study period. Baseline patient characteristics are summarized in Table 1⇓.

Patients were anticoagulated with an international normalized ratio of 2.0 to 3.0 after repair or bioprosthetic replacement, and anticoagulation was stopped after 3 months unless other indications were present. Patients with mechanical prostheses were anticoagulated for life with an international normalized ratio of 3.0 to 4.0. Patients were routinely maintained on frusemide 40 mg and amiloride 5 mg daily after surgery. Higher diuretic doses and ACE inhibitors were used only when overt clinical heart failure developed.

Angiography and Echocardiography

LVEF was measured before surgery by angiography and echocardiography and late after surgery by echocardiography. Measurement was semiquantitative, with visual estimates and calculation from echocardiographic LV dimensions by standard formulas. Mitral regurgitation was graded from 0 to 4 (none, mild, moderate, moderately severe, and severe, respectively) by pulsed-wave Doppler echocardiography.17 Mitral valve areas were calculated by continuous-wave Doppler echocardiography and the pressure half-time method.18 Mitral pathophysiology was classified as predominantly mitral regurgitation if regurgitation of grade 3 or 4 severity was present, predominantly mitral stenosis if the mitral valve area was ≤1.5 cm2 with only grade 0 or 1 mitral regurgitation, or mixed mitral valve disease if the mitral valve area was <2 cm2 with grade 2 mitral regurgitation.

Statistical Analysis

Statistical analysis was performed with the Statistical Package for Social Sciences (SPSS) Version 6.0 program. Averages are expressed as mean±SD. Cumulative survival was calculated by life-table analysis and expressed as probable survival±SE. Baseline statistics were compared by the χ2 test. Group survival was compared pairwise by use of the Wilcoxon (Gehan) statistic. Multivariate analyses of operative mortality and group survival were performed with logistic regression and Cox regression, respectively. End points for group survival statistics were all-cause death, complication-related death (including death of myocardial failure), death of myocardial failure, death of complications unrelated to myocardial failure, and the first recorded episodes of each individual complication. Myocardial failure was defined as (1) ventricular arrhythmia in patients with a history of postoperative LV failure or LVEF of ≤40% in the absence of other causes or (2) acute or chronic LV failure due primarily to myocardial failure and unrelated to postoperative myocardial infarction, requiring increased medication. Anticoagulation-related hemorrhage was included only if it warranted hospital investigation or treatment. Mitral valve failure included grade 3 or 4 mitral regurgitation, symptomatic mitral stenosis, and mitral valve thrombosis. Parameters assessed by multivariate analysis were age, sex, year of operation, type of operation, preoperative NYHA class, preoperative LV function, cause of mitral valve disease, concomitant aortic valve disease, concomitant ischemic heart disease, mitral pathophysiology, and heart rhythm.

Results

Group Differences at Baseline

Baseline characteristics were most unfavorable in the repair group with respect to age (P=.002) and in the repair and MVR/SVP groups with respect to NYHA class and LV function (P=.044) (Table 1⇑). Rheumatic origin, mitral stenosis, concomitant aortic valve disease, female sex, and atrial fibrillation were more frequent (P<.05) in the MVR groups.

Overall Survival

Overall survival at 7 years was better in the repair (71.2±5.6%, P=.022) and MVR/SVP (66.2±12.4%, P=.017) groups than the MVR/NoSVP group (63.5±3.4%). Cumulative freedom from complication-related death at 7 years was also better in the repair (80.9±4.5%, P=.017) and MVR/SVP (82.4±9.3%, P=.019) groups than the MVR/NoSVP group (68.9±3.4%) (Fig 1⇓). Repair and MVR/SVP had significant beneficial effects on all-cause death (hazard ratios, 0.43, P<.001 and 0.40, P<.05, respectively) and complication-related death (hazard ratios, 0.38, P<.001 and 0.35, P<.05, respectively) on multivariate analysis. Age ≥70 years (hazard ratio, 1.6, P<.05), NYHA class III (hazard ratio, 2.0, P<.01) or class IV (hazard ratio, 3.9, P<.0001) symptoms, and LVEF ≤40% (hazard ratio, 1.8, P<.01) were independent risk factors for poor survival (Table 2⇓).

Early (30-Day) Mortality

Early mortality was lower in the repair (1.8%, P=.046) and MVR/SVP (1.5%, P=NS) groups than in the MVR/NoSVP group (5.0%). Causes of death are shown in Table 3⇓. Multivariate analysis showed that repair reduced the risk of early death compared with MVR/NoSVP (odds ratio, 0.27, P<.05). NYHA class IV heart failure was the greatest risk factor (odds ratio, 16.2, P<.0001). No beneficial effect was seen with MVR/SVP (Table 2⇑).

Survival curves for complications of myocardial failure and systemic thromboembolism.

Asymptomatic LV impairment (LVEF ≤40% on echocardiography without clinical evidence of myocardial failure) was moderately common in late survivors in the repair, MVR/SVP, and MVR/NoSVP groups (18.4% versus 16.7% versus 17.1%, P=NS, respectively). These patients are at risk of late myocardial failure. Functional outcome in survivors was good and similar in the repair, MVR/SVP, and MVR/NoSVP groups, with 87.1% versus 78.4% versus 86.3% (P=NS), respectively, in NYHA class I or II at follow-up.

Analysis of Possible Confounding Factors

Outcome from MVR was similar between the different surgeons. Repair was performed virtually exclusively by one surgeon. Type of operation was the only variable that changed with time during the study period. The proportion of patients who underwent repair increased initially with increasing surgical experience to reach a stable plateau by 1990. Other factors, including referral policies dictating choice of surgeon and preferred type of operation, level of surgical experience with procedures other than repair, techniques of cardiac surgery and myocardial protection, valve prostheses used, and postoperative management, remained constant during the study period. Surgery before or after January 1990 was not a significant predictor of outcome on univariate or multivariate analysis. Choice of surgeon and changes in clinical practice with time are therefore unlikely to have biased our results.

Mitral stenosis was more prevalent in the MVR/NoSVP group. These patients had better demographics than those with mitral regurgitation and tended to have better outcomes. The MVR/NoSVP group had slightly better demographics than the repair and MVR/SVP groups. If anything, these differences should have biased results in favor of MVR/NoSVP, but the opposite was true. Confounding effects of these differences can therefore be discounted.

Discussion

Subvalvular Preservation Improves Survival in Mitral Valve Surgery

Mitral valve repair has been proposed as the operation of choice for mitral valve disease. If repair is not feasible, the subvalvular apparatus should be preserved during valve replacement. Several studies have shown better outcome and LV function with mitral valve repair123456 and MVR/SVP1112 compared with MVR/NoSVP. Nevertheless, doubts about the true clinical value of these more complex procedures remain. The number of comparative studies is small. Most involved small numbers of patients with repair1 or MVR/SVP,1114 did not distinguish between MVR/SVP and MVR/NoSVP,115 were not randomized, or failed to account for different baseline patient characteristics by multivariate analysis.1 Multivariate analysis in two large (>100 patients per group) comparative studies45 of repair and replacement without subvalvular preservation failed to demonstrate independent beneficial effects of repair on survival. However, LV end-diastolic pressure was the only measure of LV function used by Sand et al4 in their study of mitral regurgitation. Diastolic parameters have less prognostic value than systolic parameters such as LVEF in mitral regurgitation.1920 In a major study of angiographic and echocardiographic prognostic indicators in 409 patients with mitral regurgitation,20 LV end-diastolic pressure had no prognostic significance. It is not clear whether preoperative LV function was taken into account in the analysis by Galloway et al.5

These problems were addressed by Enriquez-Sarano et al6 in a multivariate analysis of 195 patients with repair and 214 patients with replacement. They demonstrated improved overall survival (hazard ratio, 0.39), operative mortality (odds ratio, 0.27), and late survival (hazard ratio, 0.44) with repair. Horstkotte et al12 compared MVR/SVP and MVR/NoSVP. Although each group comprised only 50 patients, the study was prospective and randomized. Six-year mortality was lower with MVR/SVP (8%) than with MVR/NoSVP (20%), suggesting a hazard ratio of 0.4. Our results were very similar and showed improved overall survival (hazard ratio, 0.43), operative mortality (odds ratio, 0.27), and late survival (hazard ratio, 0.52) with repair and improved overall survival (hazard ratio, 0.40) with MVR/SVP. All-cause death may be a less accurate measure of outcome, because results may be skewed by death of causes entirely unrelated to surgery. This was controlled for in our study by multivariate analysis of complication-related death. Although MVR/SVP had no beneficial effect on all-cause late mortality, it had an independent beneficial effect on complication-related deaths (hazard ratio, 0.39). Our study confirms the survival advantages of subvalvular preservation.

Many animal2122 and human6141523 studies have shown better maintenance of LV function with subvalvular preservation than without. Since myocardial failure is the main cause of death in mitral valve surgery,1924 this has been cited as a major reason for the improved survival. Our study confirms this. Myocardial failure was the main cause of complication-related death, and subvalvular preservation significantly reduced the risk of death of myocardial failure (hazard ratio, 0.41 for repair and 0.19 for MVR/SVP).

Repair Reduces the Risk of Complications Unrelated to Myocardial Failure

Repaired valves are less thrombogenic than mechanical replacements. Thromboembolic risks are also lower with better LV function. Long-term anticoagulation is not required for patients in sinus rhythm. Even if long-term anticoagulation is required for atrial fibrillation or poor LV function, lower levels of anticoagulation are needed than for mechanical replacements.25 Endocarditis may be less frequent in repair,2 and the prognosis is better than that for prosthetic valve endocarditis. Repair has long-term durability8 comparable to mechanical replacement.5 Our study showed independent beneficial effects of repair on complications unrelated to myocardial failure (hazard ratio, 0.70), on death due to such complications (hazard ratio, 0.23), and on thromboembolism (hazard ratio, 0.50) compared with MVR/NoSVP. These benefits were not seen with MVR/SVP. Our results provide further evidence that repair is preferable to replacement in mitral valve surgery.

Early Surgery Is Needed to Improve Outcome

Myocardial failure rates were high and similar (34% to 40% at 7 years) in all groups and were not improved by conservative surgery on multivariate analysis. Beneficial effects were demonstrable only with fatal myocardial failure (hazard ratio, 0.41 for repair and 0.19 for MVR/SVP), suggesting that subvalvular preservation reduced the severity of myocardial failure rather than preventing it. Nonfatal myocardial failure is nevertheless likely to progress and become fatal. Although our mean follow-up was only 42 months, 66 (47.8%) of the 138 patients who developed clinical myocardial failure died of it.

The inability of subvalvular preservation to prevent myocardial failure is probably due to preexisting LV impairment. Preoperative NYHA class III or IV heart failure and depressed LVEF ≤40% each independently increased the risks of clinical myocardial failure (hazard ratios, ≥3.3) and death of myocardial failure (hazard ratios, ≥3.2). These major risk factors are markers of significant LV impairment. As with most other studies,578910 >70% of our patients were in these high-risk subgroups. Early surgery before the development of severely limiting symptoms or LV impairment with ejection fraction ≤40% could therefore improve outcome markedly.

LV Impairment Is the Final Common Pathway Through Which Risk of Myocardial Failure Is Increased

The effect of mitral pathophysiology on outcome may be indirect and due mainly to the effects of stenosis, regurgitation, or their causes on preoperative LV function. When LV function was included in the multivariate analysis, mitral pathophysiology had no significant effects on postoperative myocardial failure. A similar explanation may account for the lack of prognostic significance of concomitant ischemic heart disease and aortic valve disease whose deleterious effects were curtailed by concomitant surgical correction. Bypass graft failure or aortic bioprosthesis failure could conceivably increase rates of postoperative myocardial failure and myocardial failure–related death. However, these complications usually occur late, 8 to 15 years after surgery, outside the time frame of our medium-term study. We could not assess the benefits of concomitant bypass graft surgery relative to no bypass graft surgery in patients with significant coronary stenoses because all these patients received bypass grafts.

Study Limitations

Our study was neither prospective nor randomized. However, multivariate analysis is a well-recognized method of accounting for differences in baseline characteristics. Given the mounting evidence favoring conservative mitral valve surgery, a prospective randomized control trial may no longer be considered ethical.

Our semiquantitative methods of measuring LV function may be criticized for inaccuracy. Echocardiographic measurements are operator dependent and limited by image quality. Nevertheless, visual estimates by experienced operators have acceptable reproducibility and accuracy26 and are adequate for clinical risk stratification.62027

As in the study by Horstkotte et al,12 operative mortality and thromboembolic complication rate were lower with MVR/SVP than MVR/NoSVP, but the differences did not reach statistical significance. The trend toward fewer thromboembolic complications was not explained by differences in types of prostheses, because more patients in the MVR/SVP group had mechanical replacements. Outcome should theoretically be better with repair than with MVR/SVP. Subvalvular preservation is more physiological in repair, and LV function may be better preserved. Valve thrombogenicity and anticoagulation requirements are lower than with mechanical prostheses. Valve durability is greater than with bioprostheses. However, we were unable to confirm any advantage of repair over MVR/SVP. Our MVR/SVP group was small (n=68). Larger studies of MVR/SVP will be required to resolve these issues.

Most of our patients with mitral stenosis had long-standing disease. Only 9 of 156 patients were <45 years old at operation. Our findings may not hold true for young patients with a shorter history of mitral stenosis or active disease. Patients with balloon or surgical valvotomy or with ischemic mitral regurgitation were excluded. Although this study supports conservative surgery, no direct comment can be made about the value of valvotomy for mitral stenosis or of subvalvular preservation in ischemic mitral regurgitation.

Conclusions

Subvalvular preservation improves survival in mitral valve surgery, mainly through better preservation of LV function. However, only the severity of myocardial failure and hence its associated mortality is reduced. The high incidence of myocardial failure is unchanged and is related to preoperative LV impairment. Mitral valve repair but not replacement with subvalvular preservation also reduces the risk of complications unrelated to myocardial failure. Thus, mitral valve repair should be preferred to replacement whenever feasible, and the subvalvular apparatus should be preserved if valve replacement is necessary. Conservative surgery alone is insufficient to optimize outcome. The timing of mitral valve surgery is often suboptimal, and early surgery before the development of severely limiting symptoms or demonstrable LV impairment should be encouraged.